Is weight-based IV dosing of trastuzumab preferable to SC fixed-dose in some patients? A systematic scoping review

Trastuzumab, a key treatment for HER2-positive breast cancer, is available in weight-based IV and fixed-dose (600 mg) SC formulations. While the Phase 3 HannaH trial indicated non-inferiority of the SC formulation, there is some concern that the target plasma concentration may not be reached in overweight/obese patients whereas low-body-weight patients may be at risk of toxicity.This scoping review evaluated whether overweight/obese patients are at risk of below-target exposure with fixed-dose SC trastuzumab, whether low-body-weight patients are at risk of increased toxicity, especially cardiotoxicity, and whether IV and SC trastuzumab are equivalent in terms of treatment-emergent adverse events (TEAEs) (e.g. infections). Thirty-seven publications that met the eligibility criteria were included.Body weight is not an important determinant of exposure to trastuzumab at steady state (i.e. pre-dose cycle 8); however, real-world evidence suggests that the target concentration (20 μg/mL) may not be reached with the first SC dose in overweight/obese patients. There is no evidence that low-body-weight patients are at increased risk of cardiotoxicity with SC trastuzumab, although this may be confounded by the higher rate of cardiovascular comorbidities in overweight patients. In Phase 3 trials, SC trastuzumab was associated with higher rates of ISRs, ADAs and SAEs, the latter often requiring hospitalization and occurring during adjuvant treatment when patients are not burdened by chemotherapy.The route of administration of trastuzumab (IV vs SC) in different treatment settings should be discussed with the patient, taking into account the risks and benefits associated with each route.     

A Weight Management Program Within a High School Health Center

A program for helping adolescent students manage their weight was implemented within a school-based health center to promote evidence-based practice and identify barriers to successful weight management. Voluntary student participation included 6 visits with an advanced practice registered nurse. Body mass index screenings (n = 702) and system variables for case-managed students (n = 41) were examined to identify treatment gaps. Despite a high number of eligible students (n = 250), a low percentage of students (16%) enrolled in case management services. Building effective and sustainable approaches for weight loss in this population requires adequate staffing and community resources.     

Impact of state weights on national vaccination coverage estimates from household surveys in Nigeria

National vaccination coverage estimates from household surveys are widely used in monitoring and planning of immunization programs. In Nigeria, survey-reported national coverage estimates have shown large fluctuations in the past few years. In this paper, we examine the impact of state-level survey weighting on Nigeria’s national vaccination coverage estimation. In particular, we focus three vaccination-related outcomes among children aged 12–23 months: the coverage of the third dose of diphtheria, pertussis, and tetanus vaccine (DPT3); the coverage of the first dose of measles-containing vaccine (MCV1); and the availability rate of home-based vaccination record (HBR). We compare the sample selection and weight assignment of three major survey programs in Nigeria, and show that considerable portions of the changes in survey-reported national coverage estimates can be explained by shifts in state-level weights. Our analysis demonstrates the importance of state weighting method in estimating aggregated national coverage figures and provides important context for interpreting changes in coverage estimates between surveys in the future.     

腹腔镜减重及代谢手术前进行减重的必要性

肥胖是一种慢性、复杂性疾病,腹腔镜减重手术已成为其治疗的主要手段。对于减重手术实施前是否需要进行术前减重一直存在争议,相关临床研究结果并不一致。多个回顾性的临床研究结果表明,术前减重可以显著提高减重手术效果,缩短手术和住院时间,降低术后并发症的发生率。有研究发现,术前减重可以明显降低内脏脂肪与皮下脂肪的储备,术前2周总体重(total weight loss,TWL)下降5%可使肝脏体积缩小25%,有利于降低手术操作的难度与复杂性,缩短手术时间,进而提高减重治疗效果。加速康复外科(enhanced recovery after surgery,ERAS)在近20余年发展迅速,目前已逐渐开始应用于减重及代谢外科,术前减重是减重手术加速康复策略的重要组成部分。     

Study of Silica‐Supported Chromocene Catalysts for Ethylene Polymerization

Ultrahigh molecular weight polyethylene (UHMWPE) has drawn great interest from researchers because it possesses many excellent properties such as superb strength and impact resistance, which other polyolefin cannot achieve. A silica‐supported chromocene catalyst, for the production of UHMWPE, is successfully developed. The polyethylene (PE) produced by the chromocene catalyst can achieve a molecular weight (MW) of over 3 × 10⁶ g mol^?1 with narrow molecular weight distribution (MWD) a value of approximately three. The activity calculated by Cr per unit reaches the maximum when the loading of Cr is 1.7 wt%. With the increasing loading of chromocene, the MW shows a small increase and the MWD becomes narrower. The chromocene catalyst for ethylene polymerization also shows a significant hydrogen response. With 0.01 MPa hydrogen added into the ethylene polymerization, the MW of the PE decreases immensely to only 0.7 × 10⁶ g mol^?1 and the MWD is broadened from <3 to ≈12. If the amount of hydrogen increases, the MW continues to decrease and the MWD becomes wider. The MW of the PE produced by the chromocene catalyst can be regulated easily by adjusting the amount of hydrogen.     

Maternal dietary pattern in early pregnancy is associated with gestational weight gain and hyperglycemia: A cohort study in South West of Iran

Background and aimsMaternal dietary pattern could influence on fetal health outcome. Thus, this study was conducted to evaluate the relationship between maternal dietary pattern and Gestational Weight Gain (GWG) in each trimester and hyperglycemia amongst Arab pregnant women in south-west of Iran.MethodsThis longitudinally study was performed in urban healthcare centers of south-west of Iran. Among 610 candidates, 488 pregnant women were included in the final analysis. Consequently, two diet patterns were determined by principal component analysis and the association between GWG and blood glucose level was determined using quartile regression. Using generalized linear model, a model was adjusted for pre-pregnancy BMI, maternal age, income, and education levels.ResultsTwo dietary patterns were identified as follows: “high fat –fast food” and “vegetable-fruits & protein” pattern. High adherence to “high fat –fast food” pattern was associated with higher GWG and hyperglycemia in 3rd trimester (adjusted β: 0.029 95%CI 0.012; 0.049 P = 0.001) (adjusted β: 0.029 95%CI 0.012; 0.049 P = 0.001) respectively. High tendency to “vegetable-fruits & protein” pattern was inversely associated with development of hyperglycemia in 3rd trimester. Higher SES level was associated with low adherence to “high fat-fast food” pattern.ConclusionFindings of the study revealed that, higher adherence to high -fat diet is related to excessive GWG and hyperglycemia in late pregnancy.     

The role of oxytocin in regulation of appetitive behaviour,body weight and glucose homeostasis

Obesity and its associated complications have reached epidemic proportions in the USA and also worldwide, highlighting the need for new and more effective treatments. Although the neuropeptide oxytocin (OXT) is well recognised for its peripheral effects on reproductive behaviour, the release of OXT from somatodendrites and axonal terminals within the central nervous system (CNS) is also implicated in the control of energy balance. In this review, we summarise historical data highlighting the effects of exogenous OXT as a short‐term regulator of food intake in a context‐specific manner and the receptor populations that may mediate these effects. We also describe what is known about the physiological role of endogenous OXT in the control of energy balance and whether serum and brain levels of OXT relate to obesity on a consistent basis across animal models and humans with obesity. We describe recent data on the effectiveness of chronic CNS administration of OXT to decrease food intake and weight gain or to elicit weight loss in diet‐induced obese (DIO) and genetically obese mice and rats. Of clinical importance is the finding that chronic central and peripheral OXT treatments both evoke weight loss in obese animal models with impaired leptin signalling at doses that are not associated with visceral illness, tachyphylaxis or adverse cardiovascular effects. Moreover, these results have been largely recapitulated following chronic s.c. or intranasal treatment in DIO non‐human primates (rhesus monkeys) and obese humans, respectively. We also identify plausible mechanisms that contribute to the effects of OXT on body weight and glucose homeostasis in rodents, non‐human primates and humans. We conclude by describing the ongoing challenges that remain before OXT‐based therapeutics can be used as a long‐term strategy to treat obesity in humans.